Cells were infected with a virus expressing a green fluorescent tagged version of the HIV-1 Nef protein (in green) an imaged using live cell microscopy.
DECEMBER 1, 2020 -Jimmy Dikeakos, PhD, understands why virologists like himself quickly pivoted their focus to COVID-19 when the global pandemic struck earlier this year: Vaccines and treatments were needed and the international research community responded. The issue, he said, is that countless other epidemics currently raging — and killing millions every year — have been forgotten, at least for now.
On World AIDS Day, Dikeakos points out that in 2019 roughly 38 million people around the world were living with HIV, the virus that causes AIDS. While there have been nearly double that number of COVID-19 cases in 2020 (61.3 million), 39.3 million of them have been resolved. But there are no resolved cases of HIV.
Jimmy Dikeakos and his collaborators are trying to find a cure and a vaccine for HIV at ImPaKT Facility by targeting the protein Nef and investigating its role in compromising the immune system.
“We’ve all become epidemiology experts during the pandemic,” said Dikeakos, professor at Western’s Schulich School of Medicine & Dentistry. “We watch the news, we follow the case numbers, we look at per-cent positivity rates and I think the general public has become quite informed.”
One of the numbers that always comes up with COVID-19 is resolved cases, and that’s fantastic, he said. “We don’t know all of the long-term effects of COVID-19, but a patient testing negative after being hospitalized or coming out of quarantine after 14 days is great.”
But for HIV there is no cure and no vaccine. Though progress has been made with treatments in recent years, with doctors now able to block infectivity and impede replication of the virus, the patient is never cured.
The fact that HIV can hide in parts of the body – and actually integrate into the DNA of human cells – is part of what makes finding a cure so difficult. Dikeakos is hopeful that targeting Nef will make it easier. He wants to develop small molecule inhibitors to stop Nef from doing what it does so well, which is to internalize cell surface receptors and block the immune system from killing the infected cell.
HIV is a complex retrovirus with accessory genes that produce accessory proteins such as Nef, explained Dikeakos, who starts a term as president of the Canadian Society of Virology in January. They are termed accessory because they were originally thought to be dispensable in viral replication.
But over the years, virologists have learned that patients infected with viruses expressing defective Nef proteins become less sick. It turns out that the protein, when expressed, drives the disease.
“Viruses are basically useless: They need something else to do the work because they can’t do much on their own,” said Dikeakos. “And Nef really exemplifies that. It will latch on to proteins in human cells and basically start doing things, and one of the big things it does is, by interacting with host proteins, it changes their location within a cell.”
The disruption of receptors on the cell surface signals other cells, saying, “Hey, I’m not sick. I’m not infected, do not destroy me,” he explains. This viral strategy is known as immune evasion.
If Dikeakos and his team can block immune evasion, increasing the number of receptors and keeping them on the cell surface, the immune system will be able to figure out which cells are infected and destroy them.
“What we need to do is reduce Nef proteins in patients with HIV, so we’re developing pharmacological inhibitors that block the interaction between Nef and other proteins,” said Dikeakos. “By doing so, we would accentuate and improve the immune surveillance system to better detect and destroy infected cells.”
The ImPaKT Facility gives Dikeakos and the rest of Western’s virologists, immunologists and bacteriologists, as well as their collaborators from around the world, a big boost in the fight against HIV and other pathogens.
“It’s absolutely a huge advantage to have these facilities at Western,” said Dikeakos. “Other researchers are coming in and using the space with us. There is so much collaboration because of ImPaKT. It helps everyone. It helps us. We help other researchers and we all help the world.”
And that’s why World AIDS Day is so important, says Dikeakos. Despite COVID-19, virologists need to keep their eyes on the prize.
“We need to not only remember those currently living with HIV, but the individuals we weren’t successful in saving because the therapies didn’t exist yet. We need to maintain World AIDS Day so we don’t lose sight of the goal.”
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